Hereditary spastic paraplegia (HSP) is characterized by insidiously progressive lower extremity weakness and spasticity that affects thousands of Americans and tens of thousands of individuals around the world. The disorder begins at any age. Wheelchairs are often required. HSP is classified as “uncomplicated” or “pure” if neurologic impairment is limited to progressive lower extremity spastic weakness, hypertonic urinary bladder disturbance, mild diminution of lower extremity vibration sensation and, occasionally, joint position sensation. HSP is classified as “complicated” if the impairments present in uncomplicated HSP are accompanied by other system involvement or other neurologic findings such as seizures, dementia, amyotrophy, extrapyramidal disturbance, or peripheral neuropathy, in the absence of other co-existing disorders such as diabetes mellitus.
Currently, the diagnosis of uncomplicated HSP is established by the presence of typical clinical features and the exclusion of alternative diagnostic possibilities. Clinical features of HSP include insidiously progressive, bilateral lower extremity weakness, and increased muscle tone that is maximal in the iliopsoas, hamstring, and tibialis anterior muscles; lower extremity hyperreflexia and extensor plantar responses, often accompanied by mildly impaired vibration sensation in the distal lower extremities; and family history of similarly affected individuals. Magnetic resonance imaging (MRI) of the brain and spinal cord may be normal or show thin corpus callosum and/or spinal cord atrophy. For the vast majority of subjects, hereditary spastic paraplegia is a diagnosis of exclusion. The differential diagnosis (including multiple sclerosis, structural abnormalities involving the spinal cord, B12 deficiency, adrenomyeloneuropathy and other leukodystrophies, and dopa-responsive dystonia) should be considered thoroughly.
Molecular genetic testing for mutations in the spastin and proteolipid protein (PLP) genes are available in a limited number of laboratories. Prenatal testing for other types of HSP is being investigated on a research basis.
As can be seen from the foregoing, at the present time, diagnosis of HSP is generally a process of exclusion of other disorders, and observation of family history. As with all types of exclusionary diagnosis, patients can and are misdiagnosed. What is needed is a test for the accurate diagnosis of HSP and new methods of treatment of this debilitating disease.